Advanced SearchSearch Tips
Diagnostic and Prognostic Roles of Serum Osteopontin and Osteopontin Promoter Polymorphisms in Hepatitis B-related Hepatocellular Carcinoma
facebook(new window)  Pirnt(new window) E-mail(new window) Excel Download
 Title & Authors
Diagnostic and Prognostic Roles of Serum Osteopontin and Osteopontin Promoter Polymorphisms in Hepatitis B-related Hepatocellular Carcinoma
Chimparlee, Nitinan; Chuaypen, Natthaya; Khlaiphuengsin, Apichaya; Pinjaroen, Nutcha; Payungporn, Sunchai; Poovorawan, Yong; Tangkijvanich, Pisit;
  PDF(new window)
Background: The aims of this study were to evaluate the diagnostic and prognostic roles of serum osteopontin (OPN) and single nucleotide polymorphisms (SNPs) in the OPN promoter in patients with hepatitis B-related hepatocellular carcinoma (HCC). Materials and Methods: Four groups were studied, which included 157 patients with HCC, 73 with liver cirrhosis (LC) and 97 with chronic hepatitis (CH), along with 80 healthy subjects. Serum OPN and alpha-fetoprotein (AFP) levels were measured. The SNPs -66 T/G, -156 G/ and -433 C/T within the OPN promoter were determined by direct sequencing. Results: Serum OPN levels were significantly higher in patients with HCC than in the other groups. Area under receiver operating characteristics curves in distinguishing HCC from chronic liver disease (CLD; CH and LC) were 0.782 (95% CI; 0.729-0.834) for OPN and 0.888 (95% CI; 0.850-0.927) for AFP. Using the optimal cut-off value (70 ng/mL), OPN had sensitivity and specificity of 72% and 71%, respectively. Serum OPN was superior to AFP in detecting early-stage HCC (68% vs. 46%). A combination of both markers yielded an improved sensitivity for detecting early HCC to 82%. A high OPN level was significantly correlated with advanced BCLC stage and was an independent prognostic factor for HCC. The SNPs -156 and -443 were associated with susceptibility to HCC, but were not related to overall survival. Conclusions: Serum OPN is a useful diagnostic and prognostic marker for HCC. The combined use of serum OPN and AFP improved the diagnosis of early HCC. Genetic variation in the OPN promoter is associated with the risk, but not the prognosis of HCC.
Osteopontin;alpha-fetoprotein;tumor marker;liver cancer;hepatitis B;polymorphisms;
 Cited by
Human osteopontin: Potential clinical applications in cancer (Review), International Journal of Molecular Medicine, 2017, 39, 6, 1327  crossref(new windwow)
Bramwell VH, Doig GS, Tuck AB, et al (2006). Serial plasma osteopontin levels have prognostic value in metastatic breast cancer. Clin Cancer Res, 12, 3337-43. crossref(new window)

Bruix J, Sherman M (2011). Management of hepatocellular carcinoma: an update. Hepatology, 53, 1020-2. crossref(new window)

Chen RX, Xia YH, Cui JF, et al (2010). Osteopontin, a single marker for predicting the prognosis of patients with tumornode-metastasis stage I hepatocellular carcinoma after surgical resection. J Gastroenterol Hepatol, 25, 1435-42. crossref(new window)

Cheng J, Wang W, Sun C, et al (2014). Meta-analysis of the prognostic and diagnostic significance of serum/ plasma osteopontin in hepatocellular carcinoma. J Clin Gastroenterol, 48, 806-14. crossref(new window)

Chittmittrapap S, Chieochansin T, Chaiteerakij R, et al (2013). Prevalence of aflatoxin induced p53 mutation at codon 249 (R249s) in hepatocellular carcinoma patients with and without hepatitis B surface antigen (HBsAg). Asian Pac J Cancer Prev, 14, 7675-9. crossref(new window)

Debruyne EN, Delanghe JR (2008). Diagnosing and monitoring hepatocellular carcinoma with alpha-fetoprotein: New aspects and applications. Clin Chim Acta, 395, 19-26. crossref(new window)

Denhardt DT, Giachelli CM, Rittling SR (2001). Role of osteopontin in cellular signaling and toxicant injury. Annu Rev Pharmacol Toxicol, 41, 723-49. crossref(new window)

Dong QZ, Zhang XF, Zhao Y, et al (2013). Osteopontin promoter polymorphisms at locus -443 significantly affect the metastasis and prognosis of human hepatocellular carcinoma. Hepatology, 57, 1024-34. crossref(new window)

El-Serag HB (2012). Epidemiology of viral hepatitis and hepatocellular carcinoma. Gastroenterology, 142, 1264-73 . crossref(new window)

Furger KA, Menon RK, Tuck AB, et al (2001). The functional and clinical roles of osteopontin in cancer and metastasis. Curr Mol Med, 1, 621-32. crossref(new window)

Khodavirdi AC, Song Z, Yang S, et al (2006). Increased expression of osteopontin contributes to the progression of prostate cancer. Cancer Res, 66, 883-8. crossref(new window)

Kim J, Ki SS, Lee SD, et al (2006). Elevated plasma osteopontin levels in patients with hepatocellular carcinoma. Am J Gastroenterol, 101, 2051-9. crossref(new window)

Korita PV, Wakai T, Shirai Y, et al (2008). Overexpression of osteopontin independently correlates with vascular invasion and poor prognosis in patients with hepatocellular carcinoma. Hum Pathol, 39, 1777-83. crossref(new window)

Lee HJ, Yeon JE, Suh SJ, et al (2014). Clinical utility of plasma glypican-3 and osteopontin as biomarkers of hepatocellular carcinoma. Gut and liver, 8, 177-85. crossref(new window)

Llovet JM, Bruix J (2012). Hepatocellular carcinoma. Lancet, 379, 1245-55. crossref(new window)

JM, Burroughs A, Bruix J (2003). Hepatocellular carcinoma. Lancet, 362, 1907-17. crossref(new window)

Llovet JM, Di Bisceglie AM, Bruix J, et al (2008). Design and endpoints of clinical trials in hepatocellular carcinoma. J Natl Cancer Inst, 100, 698-711. crossref(new window)

Nagoshi S (2014). Osteopontin: Versatile modulator of liver diseases. Hepatol Res, 44, 22-30. crossref(new window)

Rohde F, Rimkus C, Friederichs J, et al (2007). Expression of osteopontin, a target gene of de-regulated Wnt signaling, predicts survival in colon cancer. Int J Cancer, 121, 1717-23. crossref(new window)

Sakaki M, Makino R, Hiroishi K, et al (2010). Cyclooxygenase-2 gene promoter polymorphisms affect susceptibility to hepatitis C virus infection and disease progression. Hepatol Res, 40, 1219-26. crossref(new window)

Shang S, Plymoth A, Ge S, et al (2012). Identification of osteopontin as a novel marker for early hepatocellular carcinoma. Hepatology, 55, 483-90. crossref(new window)

Sherman M (2011). Current status of alpha-fetoprotein testing. Gastroenterol Hepatol (N Y), 7, 113-4.

Sieghart W, Wang X, Schmid K, et al (2011). Osteopontin expression predicts overall survival after liver transplantation for hepatocellular carcinoma in patients beyond the Milan criteria. J Hepatol, 54, 89-97. crossref(new window)

Simao A, Madaleno J, Silva N, et al (2015). Plasma osteopontin is a biomarker for the severity of alcoholic liver cirrhosis, not for hepatocellular carcinoma screening. BMC gastroenterology, 15, 73. crossref(new window)

Singal A, Volk ML, Waljee A, et al (2009). Meta-analysis: surveillance with ultrasound for early-stage hepatocellular carcinoma in patients with cirrhosis. Aliment Pharmacol Ther, 30, 37-47. crossref(new window)

Sopipong W, Tangkijvanich P, Payungporn S, et al (2013). The KIF1B (rs17401966) single nucleotide polymorphism is not associated with the development of HBV-related hepatocellular carcinoma in Thai patients. Asian Pac J Cancer Prev, 14, 2865-9. crossref(new window)

Spangenberg HC, Thimme R, Blum HE (2006). Serum markers of hepatocellular carcinoma. Semin Liver Dis, 26, 385-90. crossref(new window)

Taketa K (1990). Alpha-fetoprotein: reevaluation in hepatology. Hepatology, 12, 1420-32. crossref(new window)

Tangkijvanich P, Hirsch P, Theamboonlers A, et al (1999). Association of hepatitis viruses with hepatocellular carcinoma in Thailand. J Gastroenterol, 34, 227-33. crossref(new window)

Wan HG, Xu H, Gu YM, et al (2014). Comparison osteopontin vs AFP for the diagnosis of HCC: a meta-analysis. Clin Res Hepatol Gastroenterol, 38, 706-14. crossref(new window)

Wu CY, Wu MS, Chiang EP, et al (2007). Elevated plasma osteopontin associated with gastric cancer development, invasion and survival. Gut, 56, 782-9. crossref(new window)

Yuen MF, Lai CL (2005). Serological markers of liver cancer. Best Pract Res Clin Gastroenterol, 19, 91-9.

Zhang CH, Xu GL, Jia WD, et al (2012). Prognostic significance of osteopontin in hepatocellular carcinoma: a meta-analysis. Int J Cancer, 130, 2685-92. crossref(new window)

Zhou C, Zhou HJ, Zhang XF, et al (2013). Postoperative serum osteopontin level is a novel monitor for treatment response and tumor recurrence after resection of hepatitis B-related hepatocellular carcinoma. Ann Surg Oncol, 20, 929-37. crossref(new window)